Microvascular Disease Associated with Increased Risk of Amputation

A recent American Heart Association-funded study has found that microvascular disease anywhere in the body is independently associated with a higher risk of leg amputation.

After examining a cohort of more than 125,000 veterans, investigators from Vanderbilt University Medical Center found that patients with microvascular disease had a 3.7-fold increase in risk of lower limb amputation. Additionally, investigators found that with peripheral artery disease (PAD) were at a 13.9-fold increase of lower limb amputation when compared to people without the disease.

“If a patient has PAD, they have a higher risk of other cardiovascular diseases, such as heart attacks and strokes," said lead investigator Joshua A. Beckman, M.D., lead author of the study and professor of medicine and director of Vascular Medicine at Vanderbilt University Medical Center in Nashville, TN "Our study suggests that microvascular disease in any part of the body, such as the eyes, kidneys or feet (neuropathy) may be linked to decreased blood vessel function in other parts of the body, putting patients at risk for potential lower-limb amputations."


Funded by the American Heart Association Strategically Focused Research Network in Vascular Disease and the US Department of Veteran Affairs, investigators sought to determine whether people with microvascular disease or PAD, or those with both, were at an increased risk of amputation compared to their counterparts without the disease. Data from 125,674 veterans from April 2003 to Dec. 2014 was extracted using information from the Veterans Aging Cohort Study. 


The primary outcome of the study was incident lower extremity amputation. Covariates included age, sex, race/ethnicity, HIV infection, hypertension, diabetes mellitus, lipid levels, smoking status, hepatitis C infection, renal disease, BMI, total bilirubin, COPD, drug abuse or dependence, and prevalent cardiovascular disease.

Upon analyses, investigators found that 109,447 participants did not have microvascular disease or PAD, 9125 had microvascular disease only, 5313 had PAD only, and 1789 had microvascular disease and PAD. A total of 1185 amputations occurred during the study period. 



After multivariable adjustment, it was determined that presence of microvascular disease was associated was a 3.7-fold increase in risk of amputation, PAD alone conferred a 13.9-fold increase in risk, and a combination of microvascular disease and PAD was associated a 22.7-fold increase. In unadjusted analyses, microvascular disease alone was associated with a 6.8-fold increased risk, PAD alone was associated with a 19.7-fold increase, and a combination of PAD and microvascular disease was associated with a 56.9-fold increase.

"This study advances the idea that microvascular disease is a system-wide disorder rather than only affecting one part of the body," Beckman said.

Additionally, an unadjusted analysis found that microvascular disease alone was associated with a 2-fold increase in risk of major cardiovascular events, PAD alone was associated with a 2.7-fold increase, and PAD with microvascular disease was associated a 3.9-fold increase in risk. Investigators noted that this association was attenuated but remained statistically significant when adjusting for demographic characteristics, cardiovascular disease risk factors and other confounders.

This study, titled “Microvascular Disease, Peripheral Artery Disease and Amputation,” is published in Circulation.